GRANTS

GRANTS

Health

Preventing and treating addiction by elucidating how the brain deals with uncertainty

Fanny cazettes

Nationality French

Year of selection 2016

Institution Champalimaud Foundation

Country Portugal

Risk Health

Post-Doctoral Fellowship

2 years

130000 €

Whether you are trying to decide which place to order food from or when to liquidate your stocks, your brain has to weigh the options and decide with a limited knowledge of the outcome. Uncertainty is inherent in decision-making processes due to the unpredictable nature of the world. As a consequence, we often must assess tradeoffs between safe options and risky ones that have the potential to offer a great windfall. Faced with this kind of decisions, some people are more prone to taking their chances than others. For a few individuals, this propensity is exacerbated to the point where they poorly handle uncertainty and develop pathological conditions such as impulsivity, gambling problems or drug addiction. What determines whether we choose to engage in risky behaviour or not? What goes on in the brain of people who are prone to prefer risky options, regardless of the consequences? To answer these question, Dr. Fanny Cazettes is investigating how the brain deals with uncertainty when making decisions. She aims to shed light on the neuronal mechanisms involved, with a focus on the role of the neurotransmitter serotonin. The objective is to better understand behavioral adaptation in situations of uncertainty and pave the way for the development of strategies to prevent risky behaviour.

To illustrate how uncertainty comes into play when making most decisions, Dr. Fanny Cazettes gives the following example : "Imagine you've just moved to a new city and you are looking for a new house. You can choose the first one you visit or wait to know more about the market in the area : what the prices are, which other houses are available, etc. This way, after visiting a few houses, you can make a better and more informed decision. However, the more you wait, the more money you spend on hotels". "There are a lot of examples, from minor to crucial decisions, in which the brain has to ponder the level of risk associated with different options and make the right decision to ensure optimal outcome", Dr. Fanny Cazettes emphasizes. "I want to understand how brain activity guides these kind of decisions, how the different neural circuits work together to form the decision and ultimately take the action," she explains. "One major goal is to decipher why some people are more or less risk prone. This may lead to innovative therapeutic approaches to help those who are incapable of evaluating the risks associated with their behaviour."

Exploring how decisions are formed and modulated in the face of uncertainty

Dr. Fanny Cazettes' project will focus on two areas of the brain in particular : the prefrontal cortex and the premotor cortex, key regions for complex decision making as they orchestrate thoughts and action. To shed light on the brain's representation of uncertainty and the path to decision-making, Dr. Fanny Cazettes will use cutting edge technology to directly access and monitor the neural activity of mice while they are performing tasks that mimic the decision-making dilemma. "We hypothesize that there exist different neural signatures of uncertainty in the prefrontal areas responsible for outcome prediction and in motor regions involved in action selection", she explains. "We will then explore how serotonin, a neuromodulator implicated in a wide range of risky behaviours, affects representations of uncertainty in the frontal cortical regions". Specifically, Fanny Cazettes and colleagues will monitor serotonin release in the brain to investigate its role in regulating representations of uncertainty. Addictive behaviours, like other psychiatric conditions, are no longer considered to be solely psychological disorders. Scientific research shows that these conditions also originate from cognitive disfunction, causing a person to persist in doing something regardless of the risk. To prevent and treat addiction, a precise understanding of how brain mechanisms affect and are affected by these pathologies is necessary. In this sense, Dr. Fanny Cazettes' research will contribute greatly to finding therapeutical strategies for addictive and risky behaviours, notably involving the use of serotonin, a neuromodulator used in antidepressants.